Parental mosaic cutaneous‐gonadal GJB2 mutation: From epidermal nevus to inherited ichthyosis‐deafness syndrome

Abstract

Ichthyosis and deafness syndrome is a group of devastating genodermatoses caused by heterozygous mutations in GJB2, encoding the gap junction protein connexin 26. These syndromes are characterized by severe skin disease, hearing loss, recurrent infections, and cutaneous neoplasms. Cutaneous somatic mutations in the same gene are associated with porokeratotic eccrine ostial dermal duct nevus. Here we report a family in which a parent presented with localized epidermal nevus and his child suffered with hystrix‐like ichthyosis with deafness. Histologic examination of the parent's cutaneous lesion revealed verrucous epidermal nevus without features of porokeratotic eccrine ostial dermal duct nevus. Genetic analysis identified the same pathogenic variant, GJB2 c.148G>A (p.D50N), in DNA extracted from the parent's cutaneous lesion and the child's leukocytes, but not in the parent's leukocytes. This study expands the phenotypic heterogeneity of GJB2 mosaic variants in addition to porokeratotic eccrine ostial dermal duct nevus, and emphasizes the importance of molecular diagnosis of mosaic skin diseases considering the risk of severe inherited diseases in the offspring.

Nevus Sebaceous Syndrome: A Case Report and Literature Review of the Associated Neurological Complications

“…For one KEN patient, a maternally inherited duplication in the first two exons of the HUWE1 gene was found; this gene is known to be associated with neurodevelopmental and intellectual disability [52]. This literature review also captured a few conditions that are less related to NSS: A patient with giant melanocytic congenital nevi (GMCN) had an NRAS (Q61R) mutation [9], a patient with Costello Syndrome had an HRAS (G12S) mutation [10], a patient with RAVEN had a mutation in the FGFR2 gene (C382R) [11], and finally, a patient diagnosed with a verrucous epidermal nevus and hystrix-like ichthyosis was found to have mutations in the GJB2 gene, which encodes a member of the gap junction protein family [12]. Two patients were diagnosed with ENS, with no further specification of subtype.…”